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Biophysical property and broad anti-HIV activity of albuvirtide, a 3-maleimimidopropionic acid-modified peptide fusion inhibitor.

Chong H, Yao X, Zhang C, Cai L, Cui S, Wang Y, He Y - PLoS ONE (2012)

Bottom Line: The results showed that ABT had potent inhibitory activity against the subtypes A, B and C that predominate the worldwide AIDS epidemics, and subtype B', CRF07_BC and CRF01_AE recombinants that are currently circulating in China.Furthermore, ABT was also highly effective against HIV-1 variants resistant to T20.Taken together, our data indicate that the chemically modified peptide ABT can serve as an ideal HIV-1 fusion inhibitor.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

ABSTRACT
Albuvirtide (ABT) is a 3-maleimimidopropionic acid (MPA)-modified peptide HIV fusion inhibitor that can irreversibly conjugate to serum albumin. Previous studies demonstrated its in vivo long half-life and potent anti-HIV activity. Here, we focused to characterize its biophysical properties and evaluate its antiviral spectrum. In contrast to T20 (Enfuvirtide, Fuzeon), ABT was able to form a stable α-helical conformation with the target sequence and block the fusion-active six-helix bundle (6-HB) formation in a dominant-negative manner. It efficiently inhibited HIV-1 Env-mediated cell membrane fusion and virus entry. A large panel of 42 HIV-1 pseudoviruses with different genotypes were constructed and used for the antiviral evaluation. The results showed that ABT had potent inhibitory activity against the subtypes A, B and C that predominate the worldwide AIDS epidemics, and subtype B', CRF07_BC and CRF01_AE recombinants that are currently circulating in China. Furthermore, ABT was also highly effective against HIV-1 variants resistant to T20. Taken together, our data indicate that the chemically modified peptide ABT can serve as an ideal HIV-1 fusion inhibitor.

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Related in: MedlinePlus

Biophysical characterization of ABT by ITC assay.2 mM N36 dissolved in ddH20 was injected into the chamber containing 200 µM ABT, C34 or T20. The experiments were carried out at 25°C. Data acquisition and analysis were performed using MicroCal Origin software (version 7.0), and show that ABT and C34 can efficiently interact with N36 but T20 not.
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pone-0032599-g003: Biophysical characterization of ABT by ITC assay.2 mM N36 dissolved in ddH20 was injected into the chamber containing 200 µM ABT, C34 or T20. The experiments were carried out at 25°C. Data acquisition and analysis were performed using MicroCal Origin software (version 7.0), and show that ABT and C34 can efficiently interact with N36 but T20 not.

Mentions: Further, we used an ITC assay to determine the interaction between C-peptides and N36. Consistently, both ABT and C34 could specifically interact with N36 in our experimental conditions (Fig. 3). In contrast, T20 could not efficiently interact with N36 as manifested by its low Kd value compared to ABT and C34. Such biophysical characteristics of ABT indicate that this MPA-modified peptide maintains its normal structure to form α-helical interactions with the N-helices.


Biophysical property and broad anti-HIV activity of albuvirtide, a 3-maleimimidopropionic acid-modified peptide fusion inhibitor.

Chong H, Yao X, Zhang C, Cai L, Cui S, Wang Y, He Y - PLoS ONE (2012)

Biophysical characterization of ABT by ITC assay.2 mM N36 dissolved in ddH20 was injected into the chamber containing 200 µM ABT, C34 or T20. The experiments were carried out at 25°C. Data acquisition and analysis were performed using MicroCal Origin software (version 7.0), and show that ABT and C34 can efficiently interact with N36 but T20 not.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3293837&req=5

pone-0032599-g003: Biophysical characterization of ABT by ITC assay.2 mM N36 dissolved in ddH20 was injected into the chamber containing 200 µM ABT, C34 or T20. The experiments were carried out at 25°C. Data acquisition and analysis were performed using MicroCal Origin software (version 7.0), and show that ABT and C34 can efficiently interact with N36 but T20 not.
Mentions: Further, we used an ITC assay to determine the interaction between C-peptides and N36. Consistently, both ABT and C34 could specifically interact with N36 in our experimental conditions (Fig. 3). In contrast, T20 could not efficiently interact with N36 as manifested by its low Kd value compared to ABT and C34. Such biophysical characteristics of ABT indicate that this MPA-modified peptide maintains its normal structure to form α-helical interactions with the N-helices.

Bottom Line: The results showed that ABT had potent inhibitory activity against the subtypes A, B and C that predominate the worldwide AIDS epidemics, and subtype B', CRF07_BC and CRF01_AE recombinants that are currently circulating in China.Furthermore, ABT was also highly effective against HIV-1 variants resistant to T20.Taken together, our data indicate that the chemically modified peptide ABT can serve as an ideal HIV-1 fusion inhibitor.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

ABSTRACT
Albuvirtide (ABT) is a 3-maleimimidopropionic acid (MPA)-modified peptide HIV fusion inhibitor that can irreversibly conjugate to serum albumin. Previous studies demonstrated its in vivo long half-life and potent anti-HIV activity. Here, we focused to characterize its biophysical properties and evaluate its antiviral spectrum. In contrast to T20 (Enfuvirtide, Fuzeon), ABT was able to form a stable α-helical conformation with the target sequence and block the fusion-active six-helix bundle (6-HB) formation in a dominant-negative manner. It efficiently inhibited HIV-1 Env-mediated cell membrane fusion and virus entry. A large panel of 42 HIV-1 pseudoviruses with different genotypes were constructed and used for the antiviral evaluation. The results showed that ABT had potent inhibitory activity against the subtypes A, B and C that predominate the worldwide AIDS epidemics, and subtype B', CRF07_BC and CRF01_AE recombinants that are currently circulating in China. Furthermore, ABT was also highly effective against HIV-1 variants resistant to T20. Taken together, our data indicate that the chemically modified peptide ABT can serve as an ideal HIV-1 fusion inhibitor.

Show MeSH
Related in: MedlinePlus